Changes in levels of oxidative stress markers and some neuronal enzyme activities in cerebrospinal fluid of multiple sclerosis patients.

OBJECTIVES: The aim of the present study was to assess cerebrospinal fluid (CSF) levels of malondialdehyde (MDA), F2 isoprostanes (8-iso-PGF2α) and total antioxidant status (TAS) in relapsing-remitting (RR) and secondary progressive (SP) course of MS and neurological controls. These parameters were correlated with brain tissue damage parameters - neuron-specific enolase and 3´,5´-cAMP-phosphodiesterase (PDE) in CSF. METHODS: CSF samples were obtained from MS patients divided into two groups according to the disease severity (EDSS) - RR and SP course of MS. Control group composed of neurological diagnoses without demyelination and neurodegeneration. 8-iso-PGF2α and NSE levels in the CSF samples were determined using specific immunochemistry assays. MDA levels in the CSF were measured by HPLC method after reaction with thiobarbituric acid in acidic conditions. TAS and total PDE activity of CSF was determined spectrophotometrically. RESULTS: There were significant differences in CSF MDA levels between MS group and controls and also between RR and SP disease course. By contrast, CSF levels of 8-iso-PGF2α in MS group and both forms of MS were comparable to control values. In addition, the results show increased CSF levels of PDE in MS group and no changes of NSE in CSF between MS and control group. CONCLUSION: These findings point to a possibility of using the parameters of different specificity to lipid peroxidation for monitoring different stages (acute/progressive) of MS. This study support the idea, that combination of CSF markers is important for monitoring overall brain tissue pathology in MS.

Role of astrocytes in pathogenesis of multiple sclerosis and their participation in regulation of cerebral circulation.

There is about 30% higher risk of the myocardial infarction in patients diagnosed with multiple sclerosis (MS) than in people without MS. Increased risk of cardiovascular disease development positively correlates with levels of serum markers of an endothelial dysfunction, and may give rise to a global cerebral hypoperfusion. It appears that these complications precede progressive loss of axons, which mechanisms are complex and should be linked to a loss of ß2 adrenergic receptors on astrocytes of demyelinating lesions. Consequence of this deficiency, the cause of which is not known yet, is a decline in energy metabolism of axons. Moreover, the loss of these receptors is linked to a reduced redistribution of potassium ions by astrocytes, glutamate excitotoxicity and increase of calcium ion concentration in the axon with subsequent activation of necrotic processes. In addition to immunological aspects we should take into account also parameters of the functional state of endothelium when appropriate targeted therapy for patient is considered.

Recommendations for the use of prolonged-release fampridine in patients with multiple sclerosis (MS).

Prolonged-release fampridine (fampridine PR) is a potassium channel blocker that improves conductivity of signal on demyelinated axons in central nervous system. Fampridine PR has been approved to improve speed of walking in patients with multiple sclerosis. This statement provides a brief summary of data on fampridine PR and recommendations on practical use of the medication in clinical practice, prediction, and evaluation of response to treatment and patient management.